PharmGKB: The Pharmacogenomics Knowledge Base

Gene:
ADRB1
adrenergic, beta-1-, receptor

Overview

Alternate Names: OTTHUMP00000020519; beta-1-adrenergic receptor
Alternate Symbols: ADRB1R; B1AR; BETA1AR; RHR
PharmGKB Accession Id: PA38

Details

Cytogenetic Location: chr10 : q25.3
GP mRNA Boundary†: chr10 : 115793796 - 115795518
GP Gene Boundary†: chr10 : 115783796 - 115798518
Strand: plus
Product Name: beta-1-adrenergic receptor
† The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Introduction

View Full VIP Annotation

The Beta1-adrenergic receptor (Beta-1-AR) is a G-protein-coupled receptor that was first characterized by its pharmacological specificity. The gene for this receptor (ADRB1) was cloned in 1987 from a placental cDNA library and subsequently mapped to chromosome 10q24-q26 (10q25.3) [PMID: 2825170, 2154750]. The intronless gene consists of 1,714 bp and codes for a 51.3 kDa protein consisting of 477 amino acid residues. Beta-1-ARs are the predominant Beta-AR subtype expressed in cardiac tissue, where they mediate the heart rate and contractility. Beta-1-AR expression in renal, vascular, and adipose tissues is also physiologically important.

The 145 A>G (Ser49Gly) and 1165 C>G (Arg389Gly) variants are the most common and well studied in the Beta-1-AR gene. The variant at codon 49 results in increased agonist-promoted desensitization, whereas the codon 389 polymorphism alters G-protein coupling and adenylyl cyclase activity. The impact of these polymorphisms on cardiovascular disease and drug response has been the subject of numerous investigations, which were recently reviewed in detail [PMID: 16120061]. Three other validated SNPs are currently documented in dbSNP, two of which have been confirmed in resequencing efforts (SeattleSNPs). Several other SNPs have been reported but not validated [PMID: 11102996, 10794544]. The functional consequences of these other polymorphisms are unknown.

In-Depth Annotations (In-Depth Annotation)

  1. rs1801252 at chr10:115794026 in ADRB1
    This variant results in increased agonist-promoted desensitization and has been well studied for impact on cardiovascular disease and drug response.
    Variant Name:
    ADRB1:49Ser>Gly
    Related Diseases:
    Heart Diseases
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp
  2. rs1801253 at chr10:115795046 in ADRB1
    This variant results in altered G-protein coupling and adenylyl cyclase activity and has been well studied for impact on cardiovascular disease and drug response.
    Variant Name:
    ADRB1:389Arg>Gly
    Related Diseases:
    Heart Diseases
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp

Curated Annotations (Curated Annotation)

  1. rs1801252 at chr10:115794026 in ADRB1
    The haplotype defined by the A allele of this SNP and the C allele of rs1801253 is associated with increased mortality risk in hypertensive patients with documented coronary artery disease. This increased risk was observed in patients with one or two copies of the AC haplotype. Significant association of the AC haplotype with mortality risk manifested in patients who were treated with the Ca++ channel blocker verapamil, but not in patients treated with the beta-blocker atenolol. Thus, individuals with the AC haplotype may experience better outcomes from treatment with atenolol vs. treatment with verapamil. No association was observed for nonfatal myocardial infarction or nonfatal stroke.
    Variant Name:
    ADRB1:Ser49Gly (145A>G)
    Related Drugs:
    atenolol, verapamil
    Related Diseases:
    Death
    Evidence:
    PMID:18615004
  2. rs1801252 at chr10:115794026 in ADRB1
    Data from a study on forty hypertensive men and women aged 35 to 65 years suggest that this SNP together with rs1801253 in the ADRB1 gene are important determinants of antihypertensive response to metoprolol.
    Variant Name:
    ADRB1:Ser49Gly (145A>G)
    Related Drugs:
    metoprolol
    Related Diseases:
    Hypertension
    Evidence:
    PMID:12844134
  3. rs1801253 at chr10:115795046 in ADRB1
    The haplotype defined by the C allele of this SNP and the A allele of rs1801252 is associated with increased mortality risk in hypertensive patients with documented coronary artery disease. This increased risk was observed in patients with one or two copies of the AC haplotype. Significant association of the AC haplotype with mortality risk manifested in patients who were treated with the Ca++ channel blocker verapamil, but not in patients treated with the beta-blocker atenolol. Thus, individuals with the AC haplotype may experience better outcomes from treatment with atenolol vs. treatment with verapamil. No association was observed for nonfatal myocardial infarction or nonfatal stroke.
    Variant Name:
    ADRB1:Arg389Gly (1165C>G)
    Related Drugs:
    atenolol, verapamil
    Related Diseases:
    Death
    Evidence:
    PMID:18615004
  4. rs1801253 at chr10:115795046 in ADRB1
    The G/G (Gly/Gly) genotype of this SNP was associated with reduced risk of edema resulting from treatment with muraglitazar (BMS-298585) relative to the C/C (Arg/Arg) genotype. The test population consisted of patients with diabetes or hyperlipidemia.
    Related Drugs:
    muraglitazar
    Related Diseases:
    Diabetes Mellitus, Edema, Hyperlipidemias
    Evidence:
    PMID:18794727
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

Non-Curated Information

A list of non-curated publications that mention this gene along with other genes is available.

PharmGKB Curated Pathways

Curated Information

The following drugs are in curated knowledge about this gene.

  Drug Class Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
antiarrhythmics, class i and iii
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
antidepressants
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Antihypertensives
  •   
  • PD
  • PK
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
Beta Blocking Agents
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
selective beta-2-adrenoreceptor agonists
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
xenobiotics
  •   
  •   
  •   
  •   
  • GN
Publications
  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
acebutolol
  •   
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
amiodarone
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
arsenic trioxide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
atenolol
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
atropine
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
carvedilol
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
cisapride
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
disopyramide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
dobutamine
  • CO
  • PD
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
dofetilide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
droperidol
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
epinephrine
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
flecainide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
halofantrine
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
haloperidol
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
ibutilide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
lidocaine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
mesoridazine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
methadone
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
metoprolol
  •   
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
mexiletine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data No literature annotations Not annotated
muraglitazar
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
pentamidine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
pimozide
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
procainamide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
propafenone
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
quinidine
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
sotalol
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
sparfloxacin
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
thioridazine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data No literature annotations Not annotated
tocainide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
verapamil
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants

Non-Curated Information

A list of non-curated publications that mention this gene along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this gene.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Acquired Long QT Syndrome (aLQTS)
  •   
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Angina Pectoris
  •   
  • PD
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Asthma
  •   
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Cardiovascular Diseases
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Death
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
Edema
  • CO
  •   
  •   
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Heart Diseases
  •   
  •   
  •   
  •   
  •   
Variants
No phenotype data No genotype data Literature annotations available Not annotated
Heart Failure
  • CO
  •   
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Hyperlipidemias
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Hypertension
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Ischemia
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Tachycardia
  • CO
  • PD
  •   
  •   
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this gene along with other diseases is available.

Curated Phenotype Datasets

These datasets are sorted alphabetically by title.

  1. Cold Pressor Test (CPT) measurements of twins
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    Submitted by Daniel T. O'Connor, MD involving ADRB1, ADRB2 and ADRB3
  2. Drug-Induced Long QT Intervals
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    Submitted by Dan Roden, MD involving ADRB1, ADRB2, KCNE1, KCNE2, KCNH2, KCNQ1, SCN5A, almokalant, amiodarone, amitriptyline, bretylium, bupivacaine, cisapride, disopyramide, dofetilide, encainide, fluconazole, haloperidol, hydroquinidine, isoflurane, itraconazole, ketoconazole, lithium, loratadine, metoclopramide, nortriptyline, procainamide, quinidine, sematilide, sotalol, sulfamethoxazole, thioridazine, trimethoprim, , Long QT Syndrome, Proarrhythmia and Torsades de Pointes
  3. Genetic Epidemiology of Responses to Antihypertensives (GERA)
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • PD
    Submitted by Stephen T. Turner, MD involving ACE, ADD1, ADRB1, ADRB2, AGT, AGTR1, CYP11B2, GNB3, LPL, NOS3, REN, hydrochlorothiazide, and Essential hypertension
  4. Survival of patients on beta-blockers after ACS, and ADRB1, ADRB2
    • Genotype data available
    • Phenotype data available
    • No literature annotations
    • Not annotated
    • CO
    • PD
    Submitted by Howard McLeod, PharmD involving ADRB1, ADRB2, Beta Blocking Agents, , Angina, Unstable and Myocardial Infarction

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. The National Institute of Neurological Disorders and Stroke (NINDS) Repository: Cerebrovascular Disease/Stroke Study

Downloads

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LinkOuts

Entrez Gene ID:
153
OMIM Accession:
109630
607276
UCSC Genome Browser ID:
NM_000684
Ref Seq NM Accession:
NM_000684
Ref Seq NP Accession:
AAA51667
AAD53696
AAD53697
AAI69224
AAI69225
AAI69226
AAS66983
ABY87521
CAI16920
EAW49485
NP_000675
P08588
Ref Seq NT Accession:
AC_000053
AC_000142
NC_000010
NT_030059
NW_001838006
NW_924884
Ensembl ID:
ENSG00000043591
GenAtlas ID:
ADRB1
GeneCard ID:
ADRB1
SOURCE ID:
ADRB1
MutDB ID:
ADRB1
PromoLign ID:
ortho_4191
HuGE ID:
ADRB1
Comparative Toxicogenomics Acc ID:
153
ModBase:
P08588

Common Searches

Non-Curated Publications

A list of non-curated publications that mention this gene is available.

The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
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